Characterization of Candida albicans microtubules

白色念珠菌微管的表征

• 批准号: 6335826
• 负责人: LESLIE WILSON
• 金额: $ 3.86万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-15 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6335826
• 关键词: Candida albicans; SDS polyacrylamide gel electrophoresis; Saccharomyces cerevisiae; antifungal agents; binding sites; colchicine; conformation; crosslink; drug interactions; fungal proteins; guanosine diphosphate; guanosine triphosphate; method development; microtubule associated protein; microtubules; molecular dynamics; nerve /myelin protein; phosphorylation; polymerization; protein purification; protein structure; radiotracer; spirane; tau proteins; tubulin

DESCRIPTION Candida albicans, an opportunistic pathogen, can cause vaginal, oral and lung infections in immunocompromised individuals and systemic tissue damages in acquired immunodeficiency patients. The chemotherapy of C. albicans infections is limited because of the strong similarities between C. albicans cells and human cells. However, the mitotic spindles in mammalian and Candida cells are constructed differently. In addition, significant differences exist in the sequences of fungal and mammalian tubulins, which are the building block units of mitotic spindles. Little information is available at biochemical and functional levels about Candida tubulin, and virtually nothing is known regarding the polymerization and dynamics properties of Candida microtubules. The thinking is that understanding the differences between fungal cell tubulin and mammalian tubulin could lead to development of new and selective drugs for the treatment of fungal diseases. Therefore, it is proposed to develop a large-scale purification strategy for C. Albicans tubulin based upon previous success in this laboratory with tubulin from Saccharomyces cerevisiae. The tubulin will be characterized biochemically, and the polymerization and dynamic properties of Candida microtubules determined. Finally, the mechanism of interaction of two known microtubule-targeted antifungal drugs (benomyl and griseofulvin) with the Candida tubulin will be determined and the mechanisms by which the drugs modulate the polymerization and dynamics properties of the tubulin will be elucidated.

描述 白色念珠菌是一种条件致病菌，可引起阴道、口腔和肺部。 免疫受损个体的感染和全身组织损害 获得性免疫缺陷患者。白色念珠菌感染的化疗 是有限的，因为白色念珠菌细胞和 人类细胞。然而，哺乳动物和念珠菌细胞中的有丝分裂纺锤体是 不同的构造。此外，还存在显著的差异 真菌和哺乳动物的微管蛋白序列，它们是构建单元 有丝分裂纺锤体。在生物化学和生物化学网站上几乎没有什么信息 假丝酵母菌微管蛋白的功能水平，几乎一无所知 关于念珠菌微管的聚合和动力学性质。 我们的想法是，了解真菌细胞微管蛋白之间的差异 和哺乳动物微管蛋白可能导致新的和选择性的药物开发 真菌病的治疗。因此，建议开发一种 基于前人的白念珠菌微管蛋白大规模纯化策略 利用酿酒酵母中的微管蛋白在本实验室获得成功。这个 微管蛋白的生物化学表征及其聚合和动力学 测定了念珠菌微管的性质。最后，提出了一种新的运行机制 两种已知的微管靶向抗真菌药物(苯菌灵和苯菌灵)的相互作用 灰黄霉素)与假丝酵母菌微管蛋白结合，并通过 其中药物调节聚合和动力学性质 微管蛋白将被阐明。